Development of Melanoma Targeted Chemo-Thermo-Immuno-Therapy by Employing Melanogenic NPrCAP-Magnetite Nanomedicine

Abstract

Systemic target immuno-therapeutics and immune checkpoint inhibitors have been successfully introduced for high-risk unresectable white Caucasian melanomas. However, darker skinned Asian and Japanese patients do not receive these benefits, and new approaches for target therapy are urgently needed. We developed a new melanoma-targeting chemo-thermo-immuno-therapy (CTI therapy) by producing 17 melanogenesis substrates and selecting N-propionyl cysteaminylphenol (NPrCAP) through selective drug delivery and cytotoxicity to melanoma cells. NPrCAP generated reactive free radicals with tyrosinase and resulted in chemical cytotoxicity with production of many apoptotic and a few necrotic cells (chemo-immunotherapy). NPrCAP was further conjugated with magnetite nanoparticles and produced heat shock protein and necrotic cells after exposure to alternating magnetic fields (thermo-immunotherapy). The combined chemo-thermo-immuno (CTI) -therapy has been successfully tested in growth inhibition of experimental murine metastatic melanomas. Preliminary clinical trials have also shown significant regression of unresectable distant human melanomas and increased the life span of patients.